Departments of Dermatology and Pediatrics, Northwestern University's Feinberg School of Medicine, Chicago, Illinois, USA

Correspondence: Xiao-Qi Wang, Departments of Dermatology and Pediatrics, Northwestern University's Feinberg School of Medicine, 645 North Michigan Avenue, Suite 520, Chicago, Illinois 60611, USA. Email: x-wang1@northwestern.edu

Received 4 October 2004; Revised 1 December 2004; Accepted 10 December 2004.

Abstract

The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting ₅₁ integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAc23Gal13GalNAc14(NeuAc28NeuAc23)Gal14Glc1-Cer (GT1b) or NeuAc23Gal14Glc1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with ₅₁ integrin or uPAR/₅₁ integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin ₅₁.